Research is proposed to use virus mediated cell transformation to generate permanent cell lines of pancreas endocrine cells which have conditional ability to express differentiated endocrine function. This will be accomplished by infecting neonatal rat pancreas monolayer cultures with temperature sensitive mutants of the oncogenic animal virus, Simian Virus 40. Mutants in the A cistron of this virus will be used since these mutants produce transformed cell lines which display temperature dependent cell proliferation properties. Cloned mutant transformed cell lines will be characterized for (a) the presence of viral-specific features (e.g., T antigen and rescuable virus), (b)temperature dependent growth properties, and (c) temperature dependent differentiated properties. Differentiated properties to be monitored: type of hormone secreted (insulin is the most likely secretory hormone to be found), control over hormone secretion by glucose, glucagon and other secretagogues, cell hormone content, and changes in ultra-structural features of the cells during temperature shifts. In addition, transformed cells will be implanted into immune-deficient, diabetic rats to evaluate the biologic activity of these cells in vivo. The proposed research could provide homogeneous populations of each pancreatic endocrine cell type in sufficient quantity for many experiments not now possible.